| Item type |
文献 / Documents(1) |
| 公開日 |
2023-06-20 |
| アクセス権 |
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アクセス権 |
open access |
| 資源タイプ |
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資源タイプ識別子 |
http://purl.org/coar/resource_type/c_db06 |
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資源タイプ |
doctoral thesis |
| 出版社版DOI |
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関連識別子 |
https://doi.org/10.3389/fphys.2023.1102751 |
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関連名称 |
10.3389/fphys.2023.1102751 |
| 出版タイプ |
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出版タイプ |
NA |
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出版タイプResource |
http://purl.org/coar/version/c_be7fb7dd8ff6fe43 |
| タイトル |
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タイトル |
Single-cell RNA sequencing identifies Fgf23-expressing osteocytes in response to 1,25-dihydroxyvitamin D3 treatment |
| タイトル別表記 |
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その他のタイトル |
シングルセルRNAシーケンシングによる1,25-ジヒドロキシビタミンD3反応性Fgf23発現骨細胞の同定 |
| 著者 |
花井, 綾子
カワバタ, アヤコ
ナカジマ, ケンタ
マスダ, カズヒロ
ウラカワ, イタル
安倍, 正博
ヤマザキ, ユウジ
福本, 誠二
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| 抄録 |
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内容記述 |
Fibroblast growth factor 23 (FGF23), a hormone, mainly produced by osteocytes, regulates phosphate and vitamin D metabolism. By contrast, 1,25-dihydroxyvitamin D3, the active form of vitamin D, has been shown to enhance FGF23 production. While it is likely that osteocytes are heterogenous in terms of gene expression profiles, specific subpopulations of Fgf23-expressing osteocytes have not been identified. Single-cell RNA sequencing (scRNA-seq) technology can characterize the transcriptome of an individual cell. Recently, scRNA-seq has been used for bone tissue analysis. However, owing to technical difficulties associated with isolation of osteocytes, studies using scRNA-seq analysis to characterize FGF23-producing osteocytes are lacking. In this study, we characterized osteocytes secreting FGF23 from murine femurs in response to calcitriol (1,25-dihydroxyvitamin D3) using scRNA-seq. We first detected Dmp1, Mepe, and Phex expression in murine osteocytes by in situ hybridization and used these as marker genes of osteocytes. After decalcification, enzyme digestion, and removal of CD45+ cells, femoral bone cells were subjected to scRNA-seq. We identified cell clusters containing osteocytes using marker gene expression. While Fgf23 expression was observed in some osteocytes isolated from femurs of calcitriol-injected mice, no Fgf23 expression was detected in untreated mice. In addition, the expression of several genes which are known to be changed after 1,25-dihydroxyvitamin D3 treatment such as Ccnd2, Fn1, Igfbp7, Pdgfa, and Timp1 was also affected by calcitriol treatment in Fgf23-expressing osteocytes, but not in those lacking Fgf23 expression, even after calcitriol administration. Furthermore, box-and-whisker plots indicated that Fgf23 expression was observed in osteocytes with higher expression levels of the Fam20c, Dmp1, and Phex genes, whose inactivating mutations have been shown to cause FGF23-related hypophosphatemic diseases. These results indicate that osteocytes are heterogeneous with respect to their responsiveness to 1,25-dihydroxyvitamin D3, and sensitivity to 1,25-dihydroxyvitamin D3 is one of the characteristics of osteocytes with Fgf23 expression. It is likely that there is a subpopulation of osteocytes expressing several genes, including Fgf23, involved in phosphate metabolism. |
| キーワード |
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主題 |
FGF23 |
| キーワード |
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主題 |
osteocyte |
| キーワード |
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主題 |
single-cell RNA sequencing |
| キーワード |
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主題 |
femur |
| キーワード |
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主題 |
1,25- dihydroxyvitamin D3 |
| キーワード |
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主題 |
transcriptome |
| キーワード |
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主題 |
gene expression |
| キーワード |
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主題 |
1,25- dihydroxyvitamin D3 (calcitriol) |
| 書誌情報 |
en : Frontiers in Physiology
巻 14,
p. 1102751,
発行日 2023-01-27
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| 収録物ID |
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収録物識別子タイプ |
ISSN |
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収録物識別子 |
1664042X |
| 出版者 |
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出版者 |
Frontiers Media S.A. |
| 備考 |
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値 |
内容要旨・審査要旨・論文本文の公開
本論文は，著者Ayako Hanaiの学位論文として提出され，学位審査・授与の対象となっている。
学位授与者所属 : 徳島大学大学院医学研究科（医学専攻） |
| 権利情報 |
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権利情報 |
This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
| 言語 |
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言語 |
eng |
| 報告番号 |
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学位授与番号 |
甲第3705号 |
| 学位記番号 |
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値 |
甲医第1575号 |
| 学位授与年月日 |
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学位授与年月日 |
2023-03-23 |
| 学位名 |
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学位名 |
博士（医学） |
| 学位授与機関 |
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学位授与機関名 |
徳島大学 |
k3705_abstract.pdf (94.4 KB)
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